In vivo macroscopic analysis of Ca²⁺ activities in cortical astrocytes and pathological progression using a modified transgenic mouse model of neurodegenerative diseases

Abstract

The involvement of astrocytes in neurodegenerative diseases is attracting widespread attention in the neuroscience research field in terms of a potential therapeutic target. Astrocytic Ca²⁺ signals are affected by bioactive substances from damaged brain cells and can induce alterations of Ca²⁺-dependent cellular processes. Such alterations may lead to functional changes in astrocytes, including gene expression profiles and secretion of neuroprotective/neurotoxic molecules. Thus, analysis of astrocytic Ca²⁺ activities may provide clues to controlling neurodegenerative diseases. However, it is still unclear how the brain pathology affects astrocytic Ca²⁺ activities. Therefore, we here applied in vivo macroscopic imaging of astrocytic Ca²⁺ signals and fluorescence labeling of a disease marker protein to neurodegenerative disease model mice expressing Ca²⁺ sensor proteins. We found a spatiotemporal correlation between astrocytic Ca²⁺ signals and accumulation sites of the disease marker. Using this relationship as an indicator, we have started to develop a machine learning-assisted protocol to predict disease progression from astrocytic Ca²⁺ activities. These results and future analyses are expected to contribute to developing therapeutic strategies for neurodegenerative diseases.